EXTRACELLULAR MATRIX ASSEMBLY

细胞外基质对血管的正常功能起着至关重要的作用。 复杂的有机体。它与器官发生、细胞 分化、转移、神经引导、伤口愈合和 具有保护功能。的专用片状结构。 细胞外基质，即基底膜，位于各种组织的下方，是 与上面细胞的质膜密切接触。这个 这种结构的主要成分是层粘连蛋白、IV型胶原、肝素 硫酸盐蛋白多糖和肌动蛋白。这些化合物的分子结构 分子在很大程度上是由重组DNA方法和 每个分子的生物活性正在被阐明。这个 基底膜的组织结构因组织不同而不同。 在胚胎发生、伤口愈合、 血管生成以及在感染等病理状态下， 炎症和转移。人们对地下室是如何形成的知之甚少 膜是在上述生物体内合成和组装的 情况。这项建议的目的是审查以下因素 调节和以其他方式影响层粘连蛋白和粘连蛋白组装成 细胞和动物的细胞外基质。生物合成途径 对于细胞外基质分子，将在 几个细胞系因其独特的特性而被选中 特点。这些行将生成有关 层粘连蛋白和粘连蛋白的胞内和胞外命运 它们与其他细胞外基质成分的相互作用。作为一种 动物模型我们建议使用斑马鱼Brachydanio rerio。这 与其他脊椎动物相比，小型脊椎动物具有独特的优势 由于其规模，ex语料库的胚胎开发、成本和易用性 基因和生化操作。一种免疫学、 这些研究将使用生化和遗传学方法。它是 希望所取得的成果将有助于我们对 基膜在分子水平上的功能在正常发育和 病理情况。

The extracellular matrix plays a vital role in the normal function of complex organisms. It is implicated in organogenesis, cell differentiation, metastasis, neuronal guidance, wound healing and protective functions. A specialized sheet-like structure of the extracellular matrix, the basal lamina, underlies various tissues and is in intimate contact with the plasma membrane of the overlying cells. The major components of this structure are laminin, type IV collagen, heparan sulfate proteoglycan and entactin. The molecular structures of these molecules have been largely determined by recombinant DNA approaches and the biological activity of each molecule is being elucidated. The organization of the basement membrane varies with different tissues and undergoes dynamic changes during embryogenesis, wound healing, angiogenesis and in pathological states such as in infection, inflammation, and metastasis. Very little is known about how the basement membrane is synthesized and assembled in living organisms in the above situations. The purpose of this proposal is to examine the factors which regulate and otherwise influence the assembly of laminin and entactin into the extracellular matrix of cells and animals. The biosynthetic pathways for the extracellular matrix molecules will be manipulated with the aid of several cell lines that were selected for their distinctive characteristics. These lines will yield information on both the intracellular and extracellular fates of laminin and entactin as well as their interactions with other extracellular matrix components. As an animal model we propose to use the zebrafish, Brachydanio rerio . This small vertebrate organism has unique advantages over other vertebrates because of its size, ex corpora embryonic development, cost, and ease of genetic and biochemical manipulation. A combination of immunological, biochemical and genetic approaches will be used in these studies. It is hoped that the results obtained will contribute to our understanding of basal lamina function at the molecular level in normal development and in pathological conditions.